Ammonium Chloride → tert-butyl (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-fluorophenyl)-4-hydroxybutylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl 4-(tert-butyldimethylsilyloxy)-2-oxopyrrolidine-1-carboxylate (I-1) (13.6 g, 43.2 mmol) in THF (100 mL) at 0° C. under N2 was added (3-fluorophenyl)magnesium bromide (52 mL of 1 M solution in THF, 51.84 mmol) over 1 hour. The reaction mixture was stirred at 0° C. for 1 hour. Methanol (80 mL) was added to the mixture followed by NaBH4 (2.45 g, 64.8 mmol) at 0° C. The mixture was stirred at 0° C. for 1 hour then poured into 10% aqueous NH4Cl. The mixture was extracted with EtOAc, washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield tert-butyl (2R)-2-(tert-butyldimethylsilyloxy)-4-(3-fluorophenyl)-4-hydroxybutylcarbamate (I-2). 1H NMR (400 MHz, CDCl3) δ 7.33-7.28 (m, 1 H), 7.13-7.09 (m, 2 H), 6.98-6.92 (m, 1 H), 4.97-4.90 (m, 1 H), 4.82 (bs, 1 H), 4.12-4.06 (m, 1 H), 3.42-3.33 (m, 1 H), 3.22-3.17 (m, 1 H), 1.88-1.84 (m, 2 H), 1.47 (s, 9 H), 0.93 (s, 9 H), 0.11 (s, 6 H). MS m/z 436.1 (M+23)+.

Provenance & Evidence